Water soluble tomato extract protects against adverse effects of air pollution

ABSTRACT

The present invention relates to compositions comprising a water soluble tomato extract (WSTE) which may be used in maintaining cardiovascular health, lessening the risk of developing cardiovascular health problems, or reducing the likelihood of worsening an existing cardiovascular health problem in a subject exposed, or is at risk of exposure, to particulate air pollution.

BRIEF DESCRIPTION OF THE INVENTION

This invention relates to the use of a water-soluble tomato extract(“WSTE”) to protect against adverse effects of air pollution on thebody's cardiovascular system.

BACKGROUND OF THE INVENTION

Air pollution comes in many forms. A common type of pollution isreferred to as “particulate air pollution”, which contains pollution inthe form of soot, gases and other matter which are in the form of tinyparticles, termed “respirable particulate matter”. Respirableparticulate matter is categorized by size, such as below 10 or 2.5microns aerodynamic diameter (PM₁₀ or PM_(2.5), respectively), or asnanoparticles (less than 100 nm diameter, or PM_(0.1)). These particlesoften come from vehicle emissions, particularly diesel fuel, or fromdiesel-powered machinery.

It has been shown that particulate matter is able to enter the bloodstream and induce cytotoxic and inflammatory responses, and there is arecognized link between exposure to diesel emissions and cardiovasculardisease. However, the actual mechanism of how this is accomplished isstill not fully understood. See Solomon et al 2013 J. Thromb Haemost 11:325-34; Tabor et al 2016 Particle and Fibre Toxicology 13:6 DOI10.1186/s12989-016-0116-x; Lucking et al 2008 European Heart J 29:3043-3051; and Hunter et al 2014 Particle and Fibre Technology 11:62 DOI10.1186/s12989-014-0062-4.

Air pollution is a mixture of particulate matter (PM) and gaseouscomponents. Numerous studies show that exposure to PM air pollution hasadverse effect on cardiovascular health (Miller et al. 2012, Pope et al.2015). Platelet activity/reactivity is linked to an increased risk ofcardiovascular diseases especially thrombosis and will also contributeto the development of atherosclerosis. Platelet activity/reactivity canbe increased by a number of factors notably air pollution. Thus, PM hasbeen shown to promote arterial thrombosis and atherosclerosis throughincreased platelet activation.

Not all platelet anti-aggregation agents work via the same pathway, norare anti-aggregation agents responsive to all aggregation stimuli. Forexample, clopidrogel (an anti-platelet pharmaceutical used in thesecondary prevention of cardiovascular complications of atherosclerosis)can inhibit adenosine 5′-diphosphate (ADP)-induced platelet aggregationbut not platelet aggregation induced by collagen or thrombin. (see Weberet al 1999 British J Pharmacology 126: 415-420). PM may stimulateplatelet aggregation via a physical mechanism in addition to aphysiological mechanism (such as the mechanism seen in oxygenradical-induced aggregation).

Water soluble tomato extracts which are lycopene-free have beendescribed; see, e.g. WO2010/049707; WO10/049709, and WO99/55350 (all byProvexis Natural Products, Ltd). They are commercially available fromDSM Nutritional Products, Switzerland under the registered trademarkFRUITFLOW and FRUITFLOW 2. They have been described as havinganti-platelet aggregation abilities, which are presumed to be due to thepresence of nucleosides and other active agents in the extracts, such asadenosine, caffeic acid derivatives including chlorogenic acid, andflavonoids such as rutin and quercetin-3,4-glycoside.

It would be desirable to have a safe, effective nutraceutical, food orfood supplement, nutraceutical or medicament which could help amelioratethe effects of particulate air pollution.

DETAILED DESCRIPTION OF THE INVENTION

It has been found, in accordance with this invention, that a watersoluble tomato extract can protect the cardiovascular system against theadverse effects brought on by exposure to particulate air pollution.Thus, the invention concerns the use of a water soluble tomato extract(WSTE) for the maintenance of a healthy cardiovascular system, and/or toprevent platelet aggregation brought on by interaction with airpollution particulate matter.

According to a first aspect of the invention there is provided acomposition comprising a Water soluble tomato extract for use inmaintaining cardiovascular health, lessening the risk of developing acardiovascular health problem, or reducing the likelihood of worseningan existing cardiovascular health problem in a subject who is exposed,or is at risk of exposure, to particulate air pollution.

According to another aspect of this invention there is provided a methodof maintaining cardiovascular health, lessening the risk of developing acardiovascular health problem, or reducing the likelihood of worseningan existing cardiovascular health problem in a subject exposed, or is atrisk of exposure, to particulate air pollution comprising administeringa protective amount of a water soluble tomato extract prior to orconcomitant with exposure to air pollution particulate matter.

Another aspect of this invention provides the use of WSTE in themanufacture of a medicament, nutraceutical, food supplement or food foruse in maintaining cardiovascular health, lessening the risk ofdeveloping a cardiovascular health problem, or reducing the likelihoodof worsening an existing cardiovascular health problem in a subject whois exposed, or is at risk of exposure, to particulate air pollution.

Another aspect of this invention provides a dosage form comprising amedicament, nutraceutical, food supplement or food comprising aneffective amount of WSTE for protecting against the adverse effects ofparticulate air pollution.

The inventors believe that WSTE is effective for maintainingcardiovascular health because, as discussed below, WSTE decreases orminimizes the risk of platelet aggregation in a subject exposed toparticulate air pollution. Thus, according to another aspect of theinvention, there is provided a method of decreasing, or minimizing therisk of, platelet aggregation in a subject exposed to particulate airpollution comprising administering to the subject an effective amount ofWSTE prior to or during exposure to particulate air pollution.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows the effect of FRUITFLOW on the amount of aggregation(maximal % aggregation) induced by particulate matter. Details are inthe Examples.

FIG. 2 shows the effect of FRUITFLOW on the amount of aggregation(maximal % aggregation induced by particulate matter and ADP (adenosinediphosphate)

DEFINITIONS

As used in the specification and claims, the following definitionsapply:

Water Soluble Tomato Extract (“WSTE”): The WTSE used in this inventionhas the following properties:

-   -   It is water soluble at room temperature, i.e. at 25° C. In        preferred embodiments, the extracts also are soluble at lower        temperatures as well (such as 15° C., 10° C. or even as low as        4° C., although more stirring over a longer period of time may        be required). The WSTE contains substantially no, or only        negligible quantities of lycopene (less than 0.5% by dry weight,        preferably less than 0.1% by dry weight).    -   It is substantially free from water-insoluble particulate        material (i.e. less than 0.1% by dry weight, preferably less        than 0.01% by dry weight of particulate material).    -   It may be in liquid or dry forms. In some forms, such as in the        dry extract FRUITFLOW 2, the sugars have been removed, and the        extract has been concentrated.

Particulate Air Pollution: This is air pollution which containsparticles which are classified as nanoparticles, or have a particle sizeof PM₂0.5 or less. These size particles can be the result of “naturalsources” such as volcanic emission, dust storms, forest fires, smokefrom grassland fires and the like, or as a result of human activity suchas automotive emissions, manufacturing emissions or other activities,including smoking.

Cardiovascular health: This term is defined as conditions associatedwith unwanted platelet aggregation, such as: arthrosclerosis, myocardialinfarction, stroke, thrombosis, peripheral artery disease, or decreasedcerebral blood flow, and also includes diabetes (Type I or Type 2) andits associated cardiovascular problems.

Healthy Person—for purposes of this invention, a healthy person has notbeen diagnosed with, nor is aware of any cardiovascular health problemswhich are related to unwanted platelet aggregation, arthrosclerosis,myocardial infarction, stroke, thrombosis, peripheral artery disease,decreased cerebral blood flow, or diabetes (either Type 1 or Type 2).

Preferred Compositions

A preferred WSTE comprises a tomato extract which is substantiallylycopene-free, substantially heat stable and comprises water solublecompounds that have activity for preventing platelet aggregation andwhich have a molecular weight of less than 1000 daltons.

Preferably the WSTE comprises a, some or each of the water solublecompounds with activity for preventing platelet aggregation selectedfrom the group comprising:

-   -   (a) glycosylated phenolic acids or phenolic esters, or        derivatives thereof    -   (b) glycosylated flavonoids; and    -   (c) nucleosides.

It is preferred that the WSTE used according to the invention is atomato extract described in WO2010/049707. Preferably the WSTE is madeaccording to the methods described in WO2010/049707. For instance, insome embodiments the WSTE may be made according to the methods describedin FIG. 2 or 4 of WO2010/049707.

In one embodiment the WSTE is a liquid in the form of a syrup.

A preferred extract has a browning index of <0.8 AU, a pH of 4.0-4.3 anda density of 1.15-1.20 and may be prepared by the steps of:

-   -   (a) Preparing a start mix of homogenised tomato;    -   (b) Separating a water soluble fraction from fruit solids;    -   (c) filtration of the water soluble fraction to make the extract        substantially lycopene-free; and    -   (d) concentration of water soluble compounds with activity for        preventing platelet aggregation in the filtration permeate using        an evaporator.

In another embodiment sugars may be removed from the extract. It ispreferred that such extracts contain <1% sugar, and contain >95% of thewater soluble compounds with activity for preventing plateletaggregation that are contained in a start mix of homgenised tomatoesfrom which the WSTE is derived. Such extracts may be in the form ofconcentrated aqueous solutions or preferably in powder form. In a mostpreferred embodiment such an extract may be made by the steps of:

-   -   (a) Preparing a start mix of homogenised tomato fruit, wherein        the pH of the start mix does not exceed pH 5.5, the holding        temperature of the start mix does not exceed 35° C., and the        start mix is diluted with water such that it comprises less than        33% solids;    -   (b) Separating a water soluble fraction from fruit solids by a        procedure that does not raise the temperature of the fraction        above 60° C.;    -   (c) filtration of the water soluble fraction;    -   (d) removal of free sugars from the filtered water soluble        fraction; and    -   (e) concentration of water soluble compounds with activity for        preventing platelet aggregation by a procedure that does not        raise the temperature of the fraction above 60° C.;

Following step (e) the extract may be a concentrated aqueous solutioncontaining <1% sugar, and containing >95% of water soluble compoundswith activity for preventing platelet aggregation contained in the startmix. Such aqueous solutions may be dehydrated further to form a powder.

In some embodiments the WSTE may be provided in a composition thatcontains other molecules that are beneficial to human health. Forinstance, the composition may also contain nitrate or a precursor ofnitric oxide. The nitrate is preferably from a source of dietary nitrate(for instance, and purely by way of example, a water-soluble extractfrom swiss chard, rocket, spinach, rhubarb, strawberry or lettuce). Thecomposition may also comprise folic acid or a metabolite thereof (e.g.5-methoxytetrahydrofolate or tetrahydrofolate). Preferred compositionsfor use according to the present invention which comprise folic acid ora metabolite thereof and/or nitrate are described in WO2014/102546.

Subjects that benefit from WSTE treatment are preferably human subjects.The inventors have found that healthy persons and those with apre-existing cardiovascular condition can benefit from taking WSTE ifthey are at risk of being exposed to particulate air pollution.

Use in Healthy Persons

In some embodiments the person is a healthy person. In preferredembodiments where the person ingests the WSTE of this invention prior toexposure to air pollution, the ingestion occurs at least 30 minutes to 1hour prior to the exposure. In particularly preferred embodiments, theingestion occurs at least 2 or at least 3 hours prior to exposure inorder to ensure the food or food supplement containing the WSTE has beendigested and that the WSTE active ingredients have entered thecirculatory system at their optimum levels. In areas where air pollutionoccurs in sustained episodes (i.e. air pollution lasts more than oneday), the WSTE should be taken prior to the first episode and at leastdaily during the air pollution episode. In other embodiments, the WSTEis taken at least daily during the portion of the year where airpollution episodes are likely to occur.

Another embodiment of this invention is a method of maintaining healthyblood flow, or minimizing the risk of platelet aggregation in a personexposed to particulate air pollution comprising administering to theperson at risk of exposure an effective amount of WSTE prior to orduring exposure to particulate air pollution.

In another aspect of this invention the person at risk generally enjoysgood cardiovascular health, i.e. does not have known problems associatedwith cardiovascular health.

Another embodiment of this invention is the use of WSTE tonon-therapeutically maintain healthy blood flow in a healthy person atrisk of exposure to particulate matter type air pollution. Examples ofnon-therapeutic results include: decreasing the risk of appearing olderdue to skin care issues, particularly wrinkles or hardening of the skin,and/or maintaining general well-being and balance of energies due togood blood circulation.

Other uses of the WSTE of this invention include:

-   -   Maintaining healthy platelet function in the presence of air        pollution;    -   Maintaining a healthy blood circulation and blood flow in the        presence of air pollution;    -   Reducing the risk of an adverse cardiovascular condition, such        as atherosclerosis, or thrombosis in the presence of particulate        matter air pollution;    -   Reducing the severity of cardiovascular diseases when exposed to        particulate matter; and    -   Reducing the risk of cardiovascular and respiratory illness in        an air polluted environment.

Use in Persons Who Already have Cardiovascular Disease

It has also been surprisingly found that WSTE shows a synergisticanti-platelet aggregation effect in the presence of both adenosinediphosphate (ADP) and PM. ADP, a natural platelet agonist stored inplatelets, is released upon platelet activation; and it induces a stronginitiation of platelet aggregation. PM also strongly induces plateletaggregation generally, and also further promotes the plateletaggregation induced by ADP. The combination of ADP plus PM is inducing astronger platelet activation response than the sum of the individualplatelet activation responses induced by ADP or PM alone. As shown inmore detail in the Examples, we have found that WSTE inhibits both theplatelet activity induced by PM present in air pollution, andsurprisingly it also inhibits the ADP induced platelet aggregation whenpromoted by the presence of PM.

Thus the WSTE of this invention, if desired, can also be used in apopulation of people who have a history of cardiovascular healthproblems or diabetes, and therefore have ADP present in theircirculating blood, and are also at risk of exposure to particulate airpollution. Thus, another embodiment of this invention is a method ofmaintaining cardiovascular health in persons who have a history ofcardiovascular health problems and who are exposed to particulate airpollution or who are at risk of exposure to particulate air pollutioncomprising administering an effective amount of a WSTE extract to theperson prior to exposure or during exposure to the particulate airpollution.

Another aspect of this invention is the use of WSTE to protect the useragainst the harmful cardiovascular effects of air pollution, preferablyparticulate matter air pollution. A person who is exposed to such airpollution or who is at risk of exposure to such air pollution can ingestWSTE and thereby protect him/herself against cardiovascular problemsassociated with air pollution.

Another aspect of this invention is a method of decreasing the risk ofcardiovascular health problems associated with particulate air pollutioninduced platelet aggregation comprising administering WSTE to a personat risk of exposure to particulate air pollution.

Another aspect of this invention is the use of water soluble tomatoextract for the use in manufacturing a pharmaceutical or nutraceuticalcapable of maintaining cardiovascular health, lessening the risk ofdeveloping a cardiovascular health problem, or reducing the likelihoodof worsening an existing cardiovascular health problem in a person whois exposed or is at risk of exposure to particulate air pollution.

Dosages and Formulations

Doses:

Tomato Extract: Preferably, FRUITFLOW 2 (a powder form) is used,although FRUITFLOW 1 (a liquid form) may be preferable if theformulation is to be liquid. The amount of WSTE should be from 25-300mg/day preferably from 75-200 mg/day, and more preferably 125-175mg/day. In some embodiments, 100 or 150 mg/day may be consumed by asubject. The aforementioned amounts may be taken as a single once-a-daydose, or partial dosages may be taken more than once a day (i.e. 2 or 3times per day) so that the full dose is consumed. Preferred dosage formsaccording to the invention comprise 25-300 mg of WSTE, preferably 75-200mg of WSTE and more preferably 125-175 mg of WSTE.

Timing of the dosage: It is preferable to consume WTSE prior to exposureto the air pollution episode, preferably at least 2-3 hours prior, sothat the WTSE is properly metabolized and is available in thecirculatory system prior to the exposure. In other embodiments, theingestion occurs at least 30 minutes to 1 hour prior to the exposure. Inareas where air pollution occurs in sustained episodes (i.e. airpollution lasts more than one day), the WSTE should be taken prior tothe first episode and at least daily during the air pollution episode.In other embodiments, the WSTE is taken at least daily during theportion of the year where air pollution episodes are likely to occur.

Forms

In one embodiment the compositions of the invention may be in the formof a nutraceutical. The term “nutraceutical” as used herein denotesusefulness in both nutritional and pharmaceutical fields of application.Thus, nutraceutical compositions comprising WSTE can be used assupplements to food and beverages and as pharmaceutical formulations forenteral or parenteral application which may be solid formulations, suchas capsules or tablets, or liquid formulations, such as solutions orsuspensions.

The WSTE nutraceutical compositions according to the present inventionmay further contain protective hydrocolloids (such as gums, proteins,modified starches), binders, film-forming agents, encapsulatingagents/materials, wall/shell materials, matrix compounds, coatings,emulsifiers, surface active agents, solubilising agents (oils, fats,waxes, lecithins etc.), adsorbents, carriers, fillers, co-compounds,dispersing agents, wetting agents, processing aids (solvents), flowingagents, taste-masking agents, weighting agents, gelling agents,gel-forming agents, antioxidants and antimicrobials.

The nutraceutical compositions according to the present invention may bein any galenic oral form containing a conventional carrier material thatis suitable for administering to the body, e.g. in solid forms such as(additives/supplements for) food, food premix, fortified food, tablets,pills, granules, dragées, capsules and effervescent formulations, suchas powders and tablets, or in liquid forms, such as solutions, emulsionsor suspensions as e.g. beverages, pastes and oily suspensions. Thepastes may be incorporated in hard- or soft-shell capsules, whereby thecapsules feature e.g. a matrix of animal-derived gelatin, plant proteinsor ligninsulfonate.

If the nutraceutical composition is a pharmaceutical formulation thecomposition further contains pharmaceutically acceptable excipients,diluents or adjuvants. Standard techniques may be used for theirformulation, as e.g. disclosed in Remington's Pharmaceutical Sciences,20th edition Williams & Wilkins, Pa., USA. For oral administration,tablets and capsules are preferably used which contain a suitablebinding agent, e.g. gelatine or polyvinyl pyrrolidone, a suitablefiller, e.g. lactose or starch, a suitable lubricant, e.g. magnesiumstearate, and optionally further additives.

In some embodiments the compositions may be formulated for consumptionas a food or drink. Examples of such foods or drinks are dairy productsincluding, for example, margarines, spreads, butter, cheese, yoghurts ormilk-drinks.

Other examples of foods that may be fortified with WSTE include bread,cereal bars, bakery items, such as cakes and cookies, and potato chipsor crisps.

Beverages encompass non-alcoholic and alcoholic drinks as well as liquidpreparations to be added to drinking water and liquid food.Non-alcoholic drinks are e.g., soft drinks, sports drinks, fruit juices,lemonades, teas and milk-based drinks. Liquid foods are e.g., soups anddairy products.

Nutraceutical compositions containing WSTE may be added to a soft drink,an energy bar, or a candy.

The non-limiting examples are presented to further illustrate theinvention.

EXAMPLES Example 1

Reagents: Diesel Particulate Matter (Industrial Forklift, SRM2975) wasfrom National Institute of Standards and Technology (Gaithersburg, Md.,USA). Adenosine diphosphate (ADP), dimethyl sulfoxide (DMSO) andtitanium(IV) oxide (TiO2) anatase were from Sigma (Saint-Louis, Mo.).Phosphate buffered saline (PBS) was from Invitrogen (Carlsbad, Calif.).

Preparation of diesel particulate matter and TiO2: Particles weresuspended in DMSO and sonicated in a sonicating water bath for 5 min tominimize agglomeration. They were diluted at appropriate concentrationsin PBS before use.

Platelet aggregation measurements: Blood from healthy human volunteerswas collected through Safety-Multifly® needle into Sodium CitrateS-Monovette® tubes (Sarstedt, NUmbrecht, Germany). Platelet-rich plasma(PRP) was obtained by centrifugation of citrated blood at 150 g for 15min at 37° C. PRP were transferred into plastic tubes and left at 37° C.Remaining blood was centrifuged at 2000 g for 15 min at 37° C. to obtainplatelet-poor plasma (PPP). Platelet counts were determined using aSysmex cell counter (Norderstedt, Germany) and the platelet number inPRP was adjusted to 3×10⁸ platelets/mL with autologous PPP. PRP wereincubated with Fruitflow® 2 (86 μg/mL) or PBS at 37° C. for 10 min priorto stimulation. The PRP suspensions were stimulated with ADP (2.5 μM),diesel particulate matter (50 μgmL) or TiO₂ (50 μg/mL) in the presenceor absence of Fruitflow® and the platelet aggregation was monitored on aplatelet aggregometer (APACT 4004, Labitec, Ahrensburg, Germany) for 10min at 37° C. under stirring conditions. PPP was used to determine thebaseline (100% aggregation). As particles can impact the lighttransmission, PPP with diesel particulate matter (50 μg/mL) or TiO₂ (50μg/mL) was used as baseline in the presence of respectively dieselparticulate matter or TiO₂. The platelet aggregation was quantified asarea under the aggregation curve (AUC) and as the maximal percentaggregation (max % aggr.).

Results

ADP is a natural platelet agonist stored in platelets and is releasedupon platelet activation; it induces a strong initiation of plateletaggregation. Diesel particulate matter (PM) also strongly inducesplatelet aggregation. In contrast, non-polluted TiO2 particles did notinduce significant aggregation at equivalent concentrations. Moreover PMfurther promoted the platelet aggregation induced by ADP. Thecombination of ADP plus PM is inducing a stronger platelet activationresponse than the sum of the individual platelet activation responsesinduced by ADP or PM alone.

Interestingly Fruitflow® was also able to inhibit the plateletaggregation induced by PM. Thus the area under the aggregation curve(AUC) was significantly decreased by 30% from 18606 to 13079. and themaximal percent aggregation (max % aggr.) was significantly decreased by28% from 37% to 27% in the presence of Fruitflow® (Table 1 and FIG. 1).Finally, the platelet aggregation which is promoted by the combinationof ADP and PM is strongly inhibited by Fruitflow®. The area under theaggregation curve (AUC) was significantly decreased by 36% from 55622 to35511. The maximal percent aggregation (max % aggr.) was significantlydecreased by 35% from 101% to 66% in the presence of Fruitflow® (Table 1and FIG. 2)

TABLE 1 Effect of Fruitflow ® on platelet aggregation induced by airpollution particulate matter ADP + PM + PM + PM + ADP FF PM FF ADP ADP +FF AUC 27953 ± 6656 ± 18606 ± 13079 ± 55622 ± 35511 ± 4856 1246* 2207683* 3288 4297* Max 54 ± 7 18 ± 5* 37 ± 4 27 ± 1* 101 ± 7 66 ± 8* %aggr. All values are mean ± SD. ADP, Adenosine diphosphate. PM,particulate matter. FF, Fruitflow ®. AUC, area under the aggregationcurve. Max % aggr., maximal percent aggregation. *p < 0.05 significantlydifferent from the respective treatment not receiving FF (e.g. ADP vs.ADP + FF, PM vs PM + FF, PM + ADP vs PM + ADP + FF).

CONCLUSION

Fruitflow® inhibits the platelet activity induced by PM present in airpollution. Moreover, Fruitflow® also inhibits the ADP induced plateletaggregation when promoted by the presence of PM.

Thus, Fruitflow® reduces the platelet activation induced by PM whichpromote arterial thrombosis, atherosclerosis, and other cardiovasculardiseases. Fruitflow® may be particularly useful in case of alreadyelevated platelet reactivity due to stress. Furthermore, the WTSE can beused in persons with a preexisting disease such as diabetes orcardiovascular disease as the platelet reactivity which is increased bynatural platelet agonist released under stress conditions and diseasesuch as ADP are further promoted by air pollutants such as PM and can beinhibited by Fruitflow® such reducing the risk of cardiovascular eventsinduced by PM. In conclusion, Fruitflow® is able to reduce thedeleterious effects of PM on the cardiovascular system.

1. A method of maintaining cardiovascular health, lessening the risk ofdeveloping cardiovascular health problems, or reducing the likelihood ofworsening an existing cardiovascular health problem in a subjectexposed, or is at risk of exposure, to particulate air pollutioncomprising administering a composition comprising a water soluble tomatoextract (WSTE).
 2. The method according to claim 1 for use in the formof a pharmaceutical, nutraceutical, food supplement or food.
 3. Themethod according to claim 1 wherein the subject is a human subject. 4.The method according to claim 3 wherein the human subject is a healthyperson.
 5. The method according to claim 3 wherein the human subject isa person with an existing cardiovascular disease.
 6. The methodaccording to claim 1 wherein the subject is exposed, or is at risk ofexposure, to particulate air pollution which is formed as a result of:volcanic emissions, dust storms, forest fires, smoke from grasslandfires, automotive emissions, manufacturing emissions or smoking
 7. Themethod according to claim 1 wherein the WSTE comprises a tomato extractwhich is: (i) substantially lycopene-free; (ii) substantially heatstable; and (iii) comprises water soluble compounds that have activityfor preventing platelet aggregation and which have a molecular weight ofless than 1000 daltons.
 8. The method according to claim 7 wherein theWSTE comprises a, some or each of the water soluble compounds withactivity for preventing platelet aggregation selected from: (a)glycosylated phenolic acids or phenolic esters, or derivatives thereof,(b) glycosylated flavonoids; and (c) nucleosides.
 9. The methodaccording to claim 7 wherein the WSTE component has a browning index of<0.8 AU, a pH of 4.0-4.3 and a density of 1.15-1.20.
 10. The methodaccording to claim 7 wherein the WSTE component is a concentratedaqueous solution containing <1% sugar, and containing >95% of the watersoluble compounds with activity for preventing platelet aggregationcontained in a start mix of homgenised tomatoes from which the WSTE isderived.
 11. The method according to claim 7 wherein the WSTE componentcontains <1% sugar, and contains >95% of the water soluble compoundswith activity for preventing platelet aggregation contained in a startmix of homgenised tomatoes from which the WSTE is derived and which isin powder form.
 12. The method according to claim 1 wherein thecomposition comprises a quantity of WSTE which is sufficient todecrease, or minimize the risk of, platelet aggregation in the subjectexposed to particulate air pollution.
 13. A method for protectingagainst the adverse effects of particulate air pollution comprisingadministering a dosage form comprising a medicament, nutraceutical, foodsupplement or food containing an effective amount of water solubletomato extract (WSTE).
 14. The method according to claim 13 wherein thedosage form comprises 25-300 mg of WSTE.
 15. (canceled)
 16. Acomposition comprising a water soluble tomato extract (WSTE), whereinthe WSTE comprises a tomato extract which is: (i) substantiallylycopene-free; (ii) substantially heat stable; and (iii) comprises watersoluble compounds that have activity for preventing platelet aggregationand which have a molecular weight of less than 1000 Daltons.
 17. Thecomposition of claim 16, wherein the WSTE is a concentrated aqueoussolution containing <1% sugar, and containing >95% of the water solublecompounds with activity for preventing platelet aggregation contained ina start mix of homgenised tomatoes from which the WSTE is derived.
 18. Amethod of producing a composition comprising a water soluble tomatoextract (WSTE) of claim 16, comprising: (a) preparing a start mix ofhomogenised tomato; (b) separating a water soluble fraction from fruitsolids; (c) filtration of the water soluble fraction to make the extractsubstantially lycopene-free; and (d) concentration of water solublecompounds with activity for preventing platelet aggregation in thefiltration permeate using an evaporator.
 19. The method of claim 18,further comprising removal of free sugars from the filtered watersoluble fraction before concentrating the water soluble compounds.